1. Field
This disclosure is concerned generally with blood bag systems and specifically with a closed blood bag system useful for long term storage of red blood cells.
2. Prior art
The storage of red blood cells (RBCs) in containers, primarily plastic blood bags, is a well known and established practice. The RBCs are initially separated from whole blood in a container (plastic bag) by centrifugation of the whole blood. This results in a lower, denser RBC portion and an upper, lighter plasma portion. The upper plasma is then removed from the container by expressing it from an opening at the upper part of the container. The separated RBCs remaining in the container are then referred to as packed RBCs.
Packed RBCs can be stored for relatively long periods if a RBC preservation solution is then added. At present, using RBC storage solutions such as AS-1, AS-3, or SAGM, RBCs can be stored for up to 42 days and still be considered safe and useful. The bags used for long term storage of RBCs are typically made from a plastic film comprising polyvinyl chloride (PVC) plasticized with a plasticizer known as dioctylphthalate, also known as DOP. That plasticizer is also called diethylhexylphthalate, also known as DEHP, and that designation will be used in the remainder of this disclosure.
One criterion for the storability of RBCs is the amount of RBC hemolysis that occurs over time in a given RBC preservative solution. In U.S. Pat. No. 4,222,379 to D. Smith, DEHP plasticized PVC blood bags were said to be especially suitable for RBC storage after it was noted that relatively low amounts of hemolysis occurred when RBCs were stored in bags made from a film of that plastic. Although DEHP plasticized PVC blood bags had been available for many years, the above observation was made relatively recently and it led to several other disclosures based on related uses of that plasticizer system (e.g., the use of DEHP plasticized PVC inserts in a blood bag as in U.S. Pat. No. 4,301,800 to Collins and the use of DEHP in the form of an emulsion used in blood storage). See also, U.S. Pat. No. 4,451,259 to Geissler et al. disclosing the intentional use of DEHP in bags made from chlorine free polymers. Today, RBC storage systems capable of storing RBCs for the longest time (up to 42 days) continue to use blood bags made from DEHP plasticized PVC blood bags.
Unfortunately, DEHP is blood-extractable. This means that in time, especially with longer blood storage times of up to 42 days, the DEHP tends to leach into the stored blood or stored RBCs. Thus the observed benefit of using DEHP plasticized PVC containers to reduce hemolysis of RBCs stored for long periods is somewhat clouded because of concerns of DEHP contamination in a product intended for parenteral use in a human. See, for example, Blais P., DEHP IN BLOOD BAGS AND MEDICAL PLASTICS: THEIR LIMITATIONS. Canadian Research June/July 1981.
Although the exact cause of hemolysis in stored RBCs is not fully known, it is known that the expression of certain white blood cell (WBC) enzymes may contribute to RBC hemolysis, especially with time. See, for example, Hogman, CF et al., RED CELL PRESERVATION IN PROTEIN-POOR MEDIA 1. LEUKOCYTE ENZYMES AS A CAUSE OF HEMOLYSIS. Transfusion 1978, 18:233-241.
WBCs have been filtered from RBC/WBC mixtures to reduce the incidences of febrile reactions in patients receiving RBCs. See, for example, U.S. Pat. No. 4,810,378 to R. Carmen et. al. and U.S. Pat. No. 4,767,541 to L. Wisdom. However, such filtered RBCs are commonly passed into and stored in conventional DEHP plasticized PVC blood bags. This is not particularly surprising in view of the long time use and approval for blood storage of that plastic system. The relatively recent disclosures of the above-cited Smith, Collins and Geissler et al. patents provide added reasons for the continued use of that bag system for the long term storage of RBCs.
Non-DEHP/PVC plastic systems are being used for blood components other that RBCs (e.g., platelets can be stored in polyolefin bags or in bags made from a low extracting system of trioctyltrimellitate plasticized PVC as disclosed in U.S. Pat. No. 4,280,497 to Carmen et. al.). To date, however, those plastics have not been used for the long term storage of RBCs (storage of up to 42 days). Thus, to obtain the benefits of 42 day RBC storage, it has been common practice to use bags of DEHP plasticized PVC and simply accept the undesirable trade-off of continued DEHP contamination for low hemolysis (and 42 day storage).
Against the above background, we have attempted to see if the benefits of 42 day storage could be obtained without the disadvantages of DEHP contamination. Surprisingly, we have found that by combining the results of substantial WBC removal with the benefits of low blood extractable plastic films, it is now possible to obtain long term storage of RBCs without substantial contamination of the blood. Details of our findings are disclosed below.